title: Adhesion molecule L1 overexpressed under the control of the neuronal Thy-1 promoter improves myelination after peripheral nerve injury in adult mice.
abstract: L1 is an adhesion molecule favorably influencing the functional and anatomical recoveries after central nervous system (CNS) injuries. Its roles in peripheral nervous system (PNS) regeneration are less well understood. Studies using knockout mice have surprisingly revealed that L1 has a negative impact on functional nerve regeneration by inhibiting Schwann cell proliferation. To further elucidate the roles of L1 in PNS regeneration, here we used a novel transgenic mouse overexpressing L1 in neurons, but not in PNS or CNS glial cells, under the control of a neuron-specific Thy-1 promoter. Without nerve injury, the transgene expression, as compared to wild-type mice, had no effect on femoral nerve function, numbers of quadriceps motoneurons and myelinated axons in the femoral nerve but resulted in slightly reduced myelination in the sensory saphenous nerve and increased neurofilament density in myelinated axons of the quadriceps motor nerve branch. After femoral nerve injury, L1 overexpression had no impact on the time course and degree of functional recovery. Unaffected were also numbers of regenerated quadriceps motoneurons, precision of muscle reinnervation, axon numbers and internodal lengths in the regenerated nerves. Despite the lack of functional effects, myelination in the motor and sensory femoral nerve branches was significantly improved and loss of perisomatic inhibitory terminals on motoneurons was attenuated in the transgenic mice. Our results indicate that L1 is a regulator of myelination in the injured PNS and warrant studies aiming to improve function in demyelinating PNS and CNS disorders using exogenous L1.
authors.affiliation: Zentrum für Molekulare Neurobiologie, University Hospital Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
authors.forename: Daria
authors.initials: D
authors.lastname: Guseva
authors.forename: Meike
authors.initials: M
authors.lastname: Zerwas
authors.forename: Mei-Fang
authors.initials: MF
authors.lastname: Xiao
authors.forename: Igor
authors.initials: I
authors.lastname: Jakovcevski
authors.forename: Andrey
authors.initials: A
authors.lastname: Irintchev
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D015153:Blotting, Western; D005267:Femoral Nerve / Q000293:injuries* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012583:Schwann Cells / Q000378:metabolism; D018800:Thy-1 Antigens / Q000235:genetics* / Q000378:metabolism
chemical_list: D039842:Neural Cell Adhesion Molecule L1; D018800:Thy-1 Antigens